| First Author | Chopra AR | Year | 2008 |
| Journal | Science | Volume | 322 |
| Issue | 5906 | Pages | 1395-9 |
| PubMed ID | 19039140 | Mgi Jnum | J:142097 |
| Mgi Id | MGI:3820385 | Doi | 10.1126/science.1164847 |
| Citation | Chopra AR, et al. (2008) Absence of the SRC-2 coactivator results in a glycogenopathy resembling Von Gierke's disease. Science 322(5906):1395-9 |
| abstractText | Hepatic glucose production is critical for basal brain function and survival when dietary glucose is unavailable. Glucose-6-phosphatase (G6Pase) is an essential, rate-limiting enzyme that serves as a terminal gatekeeper for hepatic glucose release into the plasma. Mutations in G6Pase result in Von Gierke's disease (glycogen storage disease-1a), a potentially fatal genetic disorder. We have identified the transcriptional coactivator SRC-2 as a regulator of fasting hepatic glucose release, a function that SRC-2 performs by controlling the expression of hepatic G6Pase. SRC-2 modulates G6Pase expression directly by acting as a coactivator with the orphan nuclear receptor RORalpha. In addition, SRC-2 ablation, in both a whole-body and liver-specific manner, resulted in a Von Gierke's disease phenotype in mice. Our results position SRC-2 as a critical regulator of mammalian glucose production. |
